The Effect of Galactosamine on Rat Liver Cytochrome P-450 Activities

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Abstract
The effect of galactosamine on hepatic drug metabolizing activities was examined in rats. In the microsomal fraction, the contents of cytochrome P-450 (P-450) and cytochrome B5 (b5) and the activity of NADPH-cytochrome c reductase (reductase) were examined for 7 days after galactosamine administration. In addition, substrate metabolizing activities in damaged microsomes were examined using 4 substrates: amiopyrine, anilne, benzo(A)pyrene (B(a)P) and7-ethxycoumaine (7-EC). The contents of P-450 and b5 and the activity of reductase showed a minimal value after 3 days of galactosamine administration and then gradually increased, reaching the control level after 7 days. All 4 substrate metabolizing activities showed a similar response as the content of P-450, but the decrement among the 4 activities was not uniform. The activities of B(a)P hydroxylation and 7-EC deethylation were more impaled than thoe of aminopyrine demethylation and aniline hydroxylation. This nonuniformity as clear on the activity based on P-450. Galactosamine disturbed the population of multiple P-450 subtypes, and each P-450 subtype was damaged to the various extent by galactosamine administration.